Abstract Financial incentives for motivating changes in health behavior, particularly for smoking and other morbid habits, are increasingly being tested by health insurers, employers, and government agencies. However, a key unanswered question regarding smoking cessation is how to structure these incentive programs to maximize their (1) effectiveness; (2) acceptability to patients, underscored by the fact that programs that use ?commitment? contracts requiring individuals to invest their own money upfront are effective, but unpopular; and (3) economic sustainability, as defined by their return on investment?a major factor in public and private decision-making. Hospitalized smokers represent an important population to target for effective smoking cessation interventions because they are typically hospitalized for conditions related to tobacco use, experience a disproportionate burden of serious smoking-related illnesses?including coronary heart disease, cerebrovascular disease, emphysema, and cancer?have high rates of relapse to cigarette use after discharge, and impose $110 billion in costs on the healthcare system annually. They are high-risk for all of these reasons. Drs. Joseph Ladapo and Scott Sherman, the UCLA and NYU PIs of this proposal, are currently testing financial incentives in the first pilot randomized trial of incentives in hospitalized smokers (NCT02506829), and preliminary data show they are effective in helping smokers quit (6-month biochemically confirmed smoking cessation rate is 27% in incentive group vs. 9% in controls, P=0.02). We are near study completion. However, our pilot does not address the important question of whether goal-directed incentives (incentives weighted toward use of evidence-based therapies) or outcome-based incentives (incentives for successful achievement of an outcome, like successfully quitting) are more effective for promoting smoking cessation, and prior studies of smoking cessation incentives have emphasized only the latter. We propose a three-arm randomized controlled trial that will address this important knowledge gap among high-risk, hospitalized smokers, with implications for other serious chronic health conditions, and for smokers in ambulatory care settings. Comparing goal-directed incentives to outcome-based incentives and usual care, we will assess their impact on sustained smoking abstinence, use of evidenced-based therapy, and quality of life, and evaluate their short-term and long-term return on investment.